BDNF mediated TrkB activation contributes to the EMT progression and the poor prognosis in human salivary adenoid cystic carcinoma.

Summary Background The aim of the present study was to investigate whether the expression of Brain-Derived Neurotrophic Factor (BDNF) and its receptor Tropomyosin-related kinase B (TrkB) is correlated with the clinical progression of salivary adenoid cystic carcinoma (SACC) and whether the BDNF/TrkB axis is associated with the induction of epithelial–mesenchymal transition (EMT) in SACC cells. Method The expression of BDNF, TrkB, and E-cadherin (an EMT biomarker) in 76 primary SACC specimens and 20 normal salivary gland tissues was analyzed by immunohistochemistry. Additionally, the expression of BDNF, TrkB, and E-cadherin in SACC cell lines (SACC-83 and SACC-LM) was analyzed by RT-PCR and Western blotting. The biological role of the BDNF/TrkB axis in the EMT progression of SACC was evaluated after treatment with increased levels of BDNF and by inhibiting TrkB activity in SACC-83 cell line. The progression of SACC cells through EMT was assessed by RT-PCR, Western blotting, photography, migration and invasion assays. Results Elevated expression of TrkB (92.1%) and BDNF (89.5%), and downregulated expression of E-cadherin (47.4%) was found in SACC specimens, which was significantly correlated with the invasion and metastasis in SACC ( P P P Conclusions These results suggest that BDNF-mediated TrkB activation contributes to the EMT progression and the poor prognosis in SACC. The present study demonstrated that the BDNF/TrkB axis promotes the migration and invasion of SACC cells via EMT in vitro. Targeting the inactivation of the BDNF/TrkB axis may be a potential strategy for the treatment of SACC.